Many phases of basic physiology research, clinical research, and clinical diagnostic practice require repetitive sampling of body fluids for assay of key components. While sampling may be accomplished by repeated skin or tissue puncture, use of a catheter or cannula may be preferable in order to minimize trauma to the subject and the fluid source. Trained attendants are required for withdrawal of each timed sample, catheter flushing, and sample processing as each is collected. Knowledge of the time-course of changes in measured constituents is required to ensure that interpolation of intermittent results represents true patterns. However, continuous sampling may be acceptable or even preferred in some situations, such as in determination of total hormone secreted over time or when secretion dynamics are so rapid or erratic that punctate sampling might not capture significant changes in constituent levels. In such cases, constant withdrawal pumps can be employed, and sampling does not require constant supervision. However, these pumps are too bulky to be carried during normal activities, and the subject must be relatively immobile in order to avoid tangling the catheter. This constraint may alter hormone secretion patterns due to perturbation of the subject's lifestyle. Sophisticated miniaturized pumps with cooled sampling chambers are useful in clinical research to minimize such disturbances, but their cost precludes their use for routine diagnostic work or basic research.
U.S. Pat. No. 4,299,222 describes a self-contained suction pump consisting of an outer impermeable expansible housing, an inner collapsible elastomeric fluid collection container, a rigid semipermeable partition between the housing and the container and a water-imbibing composition interposed between the housing and the partition. The pump is activated by charging an aqueous fluid between the partition and the container. The water-imbibing composition takes up the fluid and creates hydrostatic pressure, thereby forcing the housing to expand outwardly. The evacuation of the water from between the partition and the container permits the container to expand, which creates a suction to draw liquid from an outside source into the container. However, only a small sample can be obtained at one time with this pump.
U.S. Pat. No. 3,880,164 describes an osmotically driven device for evacuating fluids from body cavities or wounds. The device comprises a fluid collection container that is divided into two compartments by a flexible water-impermeable partition and a semipermeable conduit that connects to one of the container compartments and extends to the fluid collection site. The conduit and the container compartment to which it is connected contain a solution that has a higher osmotic pressure than the body fluid to be collected. The other compartment is empty. Body fluids are drawn into the conduit and hence into the solution-filled compartment by osmosis. The influx of fluid causes the partition to displace into the empty compartment, thereby accommodating the incoming water.
Fluid-imbibing positive action pumps that dispense liquids rather than collecting them are described in U.S. Pat. Nos. 3,987,790 and 4,034,756. A commercial embodiment of the pumps described in these patents is marketed as the ALZET.RTM. minipump. The pumps consist of an outer rigid semipermeable housing, an inner collapsible bag contained within the housing and an osmotically effective solute interposed between the housing and the inner bag. Liquid to be dispensed is charged into the inner bag and the minipump is placed in a water-containing environment. Water from the environment diffuses through the housing and dissolves the solute. The osmotic pressure imbalance between the resulting solution and the water in the environment causes water to be imbibed through the housing into the space between it and the bag. This influx of water exerts pressure on the bag, causing it to collapse and the liquid charge to be squeezed therefrom through an outlet port.
Other fluid imbibing pumps for dispensing liquids are described in U.S. Pat. No. 3,845,770, in which an osmotically active solute is contained within a rigid, semipermeable membrane provided with an outlet. This pump is activated by placement in a fluid environment. However, this pump does not employ a collapsible or movable element to expel its contents; instead, as the fluid passes through the semipermeable membrane, the solute is dissolved and the saturated solution formed is pressurized as a result of the osmotic pressure generated within the semipermeable membrane. A commercial embodiment of such pumps is marketed as the OROS.RTM. elementary osmotic pump.
U.S. Pat. No. 4,474,575 discloses a self-driven pump assembly for dispensing a small amount of a liquid for a prolonged period of time. The pump assembly comprises a fluid imbibing pump, such as an ALZET or an OROS pump, mounted within a receptacle into which actuating fluid is placed. The liquid to be dispensed is contained within the fluid imbibing pump, and the fluid-filled receptacle provides the water-containing environment required for actuation of the pump, as described above for the ALZET and the OROS pumps.
Despite the development of the art, however, there remains a need to develop a pump for collecting a series of fluid samples over a period of time that is simple to use, portable, inexpensive, and does not interfere with the normal activities of the donor.